Auto-immune disease and inflammatory conditions are major health problems in the Western world and increasingly in developing countries. These diseases include Rheumatic conditions like Rheumatoid arthritis and Systemic lupus erythematosus (example of autoimmune diseases), the latter often described as a prototypic autoimmune disease, and in text books more than 80 autoimmune rheumatic diseases are described, cf. e.g. Harrison's Principles of Internal Medicine, 17th Edition, which hereby is incorporated by reference. In addition, conditions like inflammatory bowel disease, asthma and diabetes type 1 are examples of auto-immune conditions.
Interestingly and importantly, atherosclerosis and its consequences stroke, myocardial infarction, acute coronary syndromes and heart failure during recent years have been demonstrated to be inflammatory conditions, with activated inflammatory and immune competent cells typically present in the atherosclerotic plaques.
Further, also dementia including Alzheimer's disease, is characterized by chronic inflammation, which has also been demonstrated for osteoarthritis.
Treatment modalities against inflammation in these diseases vary, but in general have not been successful, with Rheumatoid arthrititis as a possible exception and there is a clear need of new types of treatment. Further, prediction by use of biomarkers is not optimal, and in many cases there is a great need of new types of treatment.
Cardiolipin (CL) is a dimeric phospholipid which is known to be present in eucarytic cells, bacteria and Archaebacteria but its functional role is only partly known, (Schlame M., 2008)1. It is more prevalent in cells with high metabolic activity, like heart and skeletal muscle, and especially in mitochondrial membranes. The presence of CL in mitochondria and bacteria is interesting from an evolutionary point of view since mitochondria are likely to have a bacterial origin, (Martin. W et al, 2001)2. Also lipoproteins including low density lipoprotein (LDL) contain CL in contrast to what has previously has been thought, and two thirds of CL are present in low density lipoprotein (LDL), (Deguchi et al, 2000)3.
CL has a unique dimeric structure, highly enriched in linoleic acid groups susceptible to oxidation (Schlame, M. et al, 2000, and Chicco, A J et al, 2007)4,5. It has been suggested to play a role in generation of an electrochemical potential for substrate transport and ATP synthesis both in bacteria and mitochondria, (Belikova, N A. et al, 2007 and Bosova L V, el at, 2007)6,7. CL that has undergone oxidation (oxCL) promotes delocalization and release of cytochrome c, predisposing to its release from mitochondria and the activation of the cell death programmes, (Chicco, A J. Et al, 2007, Gonzalzez, F. et al, 2007 and Nakagawa, Y., 2004)5,8,9.
Antibodies against CL (aCL) cause both venous and arterial thrombosis, and are known to be of major importance in rheumatic diseases, especially lupus erythematosus SLE by promoting cardiovascular disease and venous thrombosis, (Frostegard, J., 2005)10 and very high levels of aCL are also linked to cardiovascular disease CVD in the general population, (Hamsten, A. et al, 1986)11.
Annexin A5 is a member of the Annexin superfamily and has anti-thrombotic properties due to interaction with phospholipids, especially phosphatidylserine, and thus the coagulation cascade. It has recently been demonstrated that aCL decrease binding of Annexin A5 to endothelial cells and it has been suggested that Annexin A5 could have anti-atherothrombotic properties in general, (Cederholm, A. et al, 2005)12. Further, aCL cross reacts with oxidized low density lipoprotein (oxLDL), (Vaarala, O. et al, 1993)13. Since oxLDL is likely to be of major importance in atherosclerosis and is present in large amounts in the atherosclerotic lesions, (Hansson, G K., 2005)14, the association with aCL could have clinical implications.